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Novartis Tasigna(R) (nilotinib) Trial Shows Superior Results to Glivec(R) (imatinib) in Newly Diagnosed, Chronic Phase Chronic Myeloid Leukaemia

December 8, 2009

FRIMLEY, England, December 8 /PRNewswire/ –

– Nilotinib Surpassed imatinib in Key Measures of Treatment Effectiveness
in the Trial, in Patients With Newly-Diagnosed Disease(1)

– At 12-Months, Significantly Fewer Patients Progressed to Later Stages
of the Disease on nilotinib (300mg Twice-Daily and 400mg Twice-Daily) Than on
imatinib 400mg Once-Daily(1)

– Nilotinib was Generally Well Tolerated; Only a Small Number of Patients
Discontinued Due to Adverse Events(1)

– Novartis Plans to File for Use in Newly Diagnosed Patients With Ph+ CML
in the EU in 2010

In a large clinical trial, nilotinib demonstrated greater efficacy over
the current gold standard treatment, imatinib, in adult patients with newly
diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+
CML) in the chronic phase.(1)

In the first head-to-head study of these two oral treatments as initial
therapy for this life-threatening leukaemia, nilotinib demonstrated
statistically significant improvement over imatinib in key measures of
effectiveness used in the trial.(1) These new data were presented as a late
breaker abstract at the 51st annual meeting of the American Society of
Haematology (ASH), held 5-8 December 2009, in New Orleans, USA.(1)

CML accounts for more than one in six leukaemias in adults, with around
600 new cases being registered in England and Wales each year.(2) The
estimated prevalence of CML in 2003 in England and Wales was 2,660
patients.(2)

The trial showed that at 12 months, significantly fewer patients on
nilotinib 300mg twice-daily progressed from the initial chronic phase of the
disease to the later accelerated or blast crisis phases than those on
imatinib 400mg once-daily.(1) This demonstrates that nilotinib provided
significantly better control of the disease compared to imatinib.

Nilotinib was generally well tolerated in the study.(1) A small number of
patients discontinued due to adverse events.(1)

“The impressive rates of response observed in this study, combined with
the very low rate of disease progression seen in nilotinib-treated patients
are very encouraging,” said Professor Richard Clark, Consultant Haematologist
at Royal Liverpool University Hospital and a trialist involved in this study.
“Continued improvement in the treatment of Ph+ CML is very important and
these results indicate that nilotinib may provide long-term improvement in
progression-free survival.”

95% of patients with CML have an abnormality known as the Philadelphia
chromosome. This chromosome produces a type of protein called Bcr-Abl, which
is responsible for the overproduction of the cancerous white blood cells that
are the main feature in Ph+ CML.(3) Nilotinib is a potent and selective
inhibitor of the Bcr-Abl protein, thereby inhibiting the production of these
cancerous cells.(4,5)

“Novartis has been at the forefront of research on the molecular origin
of Ph+ CML and this has led to the development of treatments with
unprecedented effectiveness and safety,” said Panos Alexakos, Oncology
Business Unit Head for Novartis UK. “These data are exciting and the deeper
molecular response demonstrated provides hope for further improvement in
outcomes for patients with Ph+ CML in the future.”

Novartis plans to file worldwide applications for approval of nilotinib
as a treatment for adult patients with newly diagnosed Ph+ CML. Nilotinib is
currently approved in more than 80 countries including the European Union
(EU), United States and other countries for the treatment of adult patients
with Ph+ CML in chronic phase or accelerated phase who are resistant or
intolerant to prior treatment including imatinib.

Notes to editors

Study details

The clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical
Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is a Phase III
randomised, open-label, multicentre trial comparing the efficacy and safety
of nilotinib versus imatinib in adult patients with newly diagnosed Ph+ CML
in the chronic phase.(1) It is the largest global randomised comparison of
two oral therapies ever conducted in newly diagnosed Ph+ CML patients.

ENESTnd is being conducted at 220 global sites, including five sites in
the UK, in total 846 patients are enrolled. Patients were randomised to
receive nilotinib 400mg twice-daily (n = 281), nilotinib 300mg twice-daily (n
= 282) or imatinib 400mg once-daily (n = 283).(1) The primary endpoint was
MMR at 12 months; a secondary endpoint was CCyR by 12 months. It is planned
that patients are followed up for five years. Patients on the imatinib
treatment arm who had suboptimal response or treatment failure will be able
to escalate dose and/or switch to nilotinib via a protocol extension.

One of the key effectiveness measures used in the study was called major
molecular response (MMR). This is defined as the reduction in levels of the
Bcr-Abl protein to less than or equal to 0.1% of the level seen before
treatment. MMR is an important measure in CML, as data show that patients who
achieve MMR are unlikely to progress to the later stages of the disease.(6)
With nilotinib 300mg twice-daily, the rate of MMR at 12 months was twice that
of patients receiving imatinib 400mg once-daily (44% vs. 22%, p < 0.0001).(1)

Another effectiveness measure used in the study was called complete
cytogenetic response (CCyR). CCyR indicates that no CML cells containing the
Ph chromosome can be seen in a sample of bone marrow taken from the patient.
80% of patients achieved CCyR with nilotinib versus 65% with imatinib 400mg
once-daily (p < 0.0001).(1) Responses were achieved faster in the nilotinib
group than in the imatinib group.(1)

All patients had a minimum of 12 months of treatment or discontinued
early; the median follow-up was 14 months. Overall, 84%, 82% and 79% of
patients remained in the study on nilotinib 300mg twice-daily, nilotinib
400mg twice-daily and imatinib 400mg once-daily, respectively.(1)

About Ph+ CML

CML is a disease in which the body produces cancerous (leukaemic) white
blood cells. 95% of patients with CML have an abnormality known as the
Philadelphia chromosome. This chromosome produces a protein called Bcr-Abl,
which is responsible for the proliferation of leukaemic white blood cells in
Ph+ CML.(3)

CML accounts for more than one in six leukaemias in adults, with around
600 new cases being registered in England and Wales each year.(2) The
estimated prevalence of CML in 2003 in England and Wales was 2,660
patients.(2)

About Tasigna (nilotinib)

Nilotinib, a second generation TKI, is a potent and selective inhibitor
of the Bcr-Abl protein, which is responsible for the proliferation of
leukaemic white blood cells in Ph+ CML.(4,5) Nilotinib is indicated for the
treatment of adults with chronic phase and accelerated phase Ph+ CML with
resistance or intolerance to prior therapy including imatinib. Efficacy data
in patients with CML in blast crisis are not available.(5)

For nilotinib summary of product characteristics, please see:
http://emc.medicines.org.uk/medicine/20827/SPC/
Tasigna%20200%20mg%20hard%20capsules

(Due to the length of this URL, it may be necessary to copy and paste
this hyperlink into your Internet browser’s URL address field. Remove the
space if one exists.)

About Glivec (imatinib)(7)

Imatinib is approved in the EU for the treatment of all phases of Ph+
CML. Imatinib is also indicated for the treatment of adult patients with Kit
(CD 117) positive unresectable and/or metastatic malignant gastrointestinal
stromal tumours (GIST) and the adjuvant treatment of adult patients who are
at significant risk of relapse following resection of Kit (CD117)-positive
GIST.

Furthermore, imatinib is approved for the treatment of adult patients
with newly diagnosed Philadelphia chromosome positive acute lymphoblastic
leukaemia (Ph+ ALL) integrated with chemotherapy, adult patients with
relapsed or refractory Ph+ ALL as monotherapy, adult patients with
myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with
platelet-derived growth factor receptor (PDGFR) gene re-arrangements, adult
patients with advanced hypereosinophilic syndrome (HES) and/or chronic
eosinophilic leukaemia (CEL) with FIP1L1-PDGFR alpha rearrangement and the
treatment of adult patients with unresectable dermatofibrosarcoma protuberans
(DFSP) and adult patients with recurrent and/or metastatic DFSP who are not
eligible for surgery.

    For imatinib summary of product characteristics, please see:

http://emc.medicines.org.uk/document.aspx?documentId=15014

    References

    (1) Saglio G, Kim DW, Issaragrisil S, Philipp le Coutre, et al.
        Nilotinib Demonstrates Superior Efficacy Compared with Imatinib in
        Patients with Newly Diagnosed Chronic Myeloid Leukaemia in Chronic
        Phase: Results from the International Randomized Phase III ENESTnd
        Trial. American Society of Hematology 2009. Abstract number LBA-1

    (2) NICE Guidance on the use of imatinib for chronic myeloid leukaemia
        - Technology Appraisal 70. October 2003

    (3) Faderl S; Talpaz M; Estrov Z; O'Brien S; Kurzrock R; Kantarjian HM.
        The biology of chronic myeloid leukemia. N Engl J Med. 341:164-72,
        1999.

    (4) National Cancer Institute. General Information about Chronic
        Myelogenous Leukaemia (PDQ).

http://www.cancer.gov/cancertopics/pdq/treatment/CML/patient/.

        Accessed March 2009.l 1: definition of PCR.

    (5) Tasigna (nilotinib) European Summary of Characteristics. Novartis AG.

http://emc.medicines.org.uk/medicine/20827/SPC/Tasigna%20200%20mg%

        20hard%20capsules. 21/09/2009

        (Due to the length of this URL, it may be necessary to copy and paste
        this hyperlink into your Internet browser's URL address field. Remove
        the space if one exists.)

    (6) Hughes et al. Reduction of BCR-ABL Transcript Levels at 6, 12, and
        18 Months (mo) Correlates with Long-Term Outcomes on Imatinib (IM) at
        72 Mo: An Analysis from the International Randomized Study of
        Interferon versus STI571 (IRIS) in Patients (pts) with Chronic Phase
        Chronic Myeloid Leukemia (CML-CP). ASH. 2008. Abstract #334

    (7) Glivec (imatinib) European Summary of Characteristics. Novartis AG.

http://emc.medicines.org.uk/document.aspx?documentId=15014.

        03/06/2009

SOURCE Novartis Oncology


Source: newswire



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